1

OVERVIEW OF OBESITY MANAGEMENT

Caroline M. Apovian, MD, FACN, FACP, FTOS, DABOMPast President, 2018The Obesity Society

Co-Director, Center for Weight Management and Wellness

Division of Endocrinology, Diabetes, and Hypertension

Brigham and Women’s Hospital

Faculty Member

Harvard Medical School

2

Caroline M. Apovian, MD, FACN, FACP, FTOS, DABOM

• One of the founding creators of the American Board of Obesity Medicine (ABOM)

• Co-Director for the NIH-funded Boston Nutrition and Obesity Research Center (BNORC)

• President of The Obesity Society in 2017-2018

• Chair of the Endocrine Society Guidelines for Medical Treatment of Obesity, 2015

• Member of the expert panel for updating the 2013 AHA/ACC/TOS Clinical Guidelines for

the Management of Overweight and Obesity in Adults

• Former Nutrition Consultant for the National Aeronautics and Space Administration (NASA)

• Given over 200 invited lectures nationally and internationally

• Published over ten books and over 200 peer-reviewed original research and review articles

on obesity and nutrition

Current research interests are weight change and its effects on adipose tissue metabolism

and inflammation, obesity and cardiovascular disease, resolution of type 2 diabetes and

cardiovascular disease in the bariatric surgery population, disparities in the treatment of

obesity in underserved populations, and novel pharmacotherapeutic agents for the

treatment of obesity.

She is also an expert in sampling subcutaneous adipose tissue and muscle tissue in

humans and has been studying the relationship between adipose tissue inflammation and

obesity for over 15 years

3

Disclosures• Consultant, Merck

• Consultant, Nutrisystem

• Consultant, Zafgen

• Consultant, Sanofi-Aventis

• Consultant, Orexigen

• Consultant EnteroMedics

• Consultant, Scientific Intake

• Consultant, Set Point health

• Consultant, Rhythm Pharmaceuticals

• Consultant, Xeno Biosciences

• Consultant, Gelesis

• Consultant, Ferring

• Consultant, Takeda

• Consultant, Novo Nordisk

• Research support, Aspire Bariatrics

• Research support, GI Dynamics

• Research support, Pfizer

• Research support, Gelesis

• Research support, Orexigen

• Research support, Meta Proteomics

• Research support, Takeda

• Research support, The Atkins Foundation

• Research support MYOS Corporation

4

Objectives

• Identify the role of hormonal adaptation in weight management

• Name the newest anti-obesity FDA-approved medication and it’s mechanism of action

5

U.S. Prevalence of Obesity, 2017-2018

https://www.cdc.gov/nchs/products/databriefs/db360.htm

Adults > 20 years, Obesity = BMI > 30

42.4%TOTAL

43%MEN

41.9%WOMEN

6

42.4%ObesityBMI > 30

9.2%Severe ObesityBMI > 40

30.7% OverweightBMI = 25-29.9

U.S. Trends in Overweight, Obesity, and Severe ObesityAdults > 20 years

https://www.cdc.gov/nchs/data/hestat/obesity-adult-17-18/obesity-adult.htm

7

BMI: <18.5 18.5-24.9 25.0-29.9 30.0-34.9 >35 >40

Underweight Normal Overweight Obesity I Obesity II Obesity III

Weight Classifications by Body Mass Index (BMI)

https://www.cdc.gov/healthyweight/assessing/index.html

Begins at BMI > 25 kg/m2

Eligibility starts for

MEDICATIONSBMI >27 kg/m2

Eligibility starts for

SURGERYBMI >30 kg/m2

8

BMI: <18.5 18.5-24.9 25.0-29.9 30.0-34.9 >35 >40

Underweight Normal Overweight Obesity I Obesity II Obesity III

Anti-obesity Drug Treatment Criteria by BMI

Apovian CM, et al. Obesity (Silver Spring). 2019;27(2):190-204.

BMI >27 kg/m2

with ≥1 comorbidityBMI >30 kg/m2

with no comorbidities

Begins at BMI > 27

9

BMI: <18.5 18.5-24.9 25.0-29.9 30.0-34.9 >35 >40

Underweight Normal Overweight Obesity I Obesity II Obesity III

Bariatric Surgery Criteria by BMI

with Diabetes or Metabolic Syndrome

with ≥1 severe obesity-associated

comorbidity

with Diabetes or Metabolic Syndrome

with no comorbidities

Apovian CM, Aronne LJ, Bessesen D, et al. J Clin Endocrinol Metab. 2015 Feb;100(2):342-62.ASMBS Statements/Guidelines | Volume 14, Issue 8, p1071-1087, August 01, 2018

Begins at BMI > 30

10

Why Treat Obesity?

11

Designation of Obesity as a Disease

1. ASMBS, TOS, ASBP, AACE Joint Statement. Obesity is a disease: leading obesity groups agree. June 19, 2013.

http://asmbs.org/2013/06/obesity-is-a-disease-leading-obesity-groups-agree/. Accessed September 11, 2013.

2. American Medical Association. AMA Resolution No. 420 (A-13). June 19, 2013.

www.ama-assn.org/assets/meeting/2013a/a13-addendum-refcomm-d.pdf.

Medical Associations and Societies1

World / National Health Organizations1,2

• American Association of Clinical Endocrinologists

• American Academy of Family Physicians

• American College of Cardiology

• American College of Surgeons

• American Medical Association

• American Society for Reproductive Medicine

• American Urological Association

• The Endocrine Society

• The Obesity Society

• The Society for Cardiovascular Angiography and Interventions

• World Health Organization

• Food and Drug Administration

• National Institutes of Health

Obesity is a disease: leading obesity groups agree

June 19

2013

12

Consequences of Obesity

• Individuals with obesity are at

increased risk for multiple physical

and psychological morbidities

• Obesity also has adverse effects

on quality of life, disability, and

productivity

• Economic burden of obesity is

borne by patients, health care

providers, insurers, and taxpayers

Kabiri M, et al. Obesity. 2020;28:429-436.

Memory/cognitive problems

Sleep problems

Hypertension

Type 2 diabetes

Tumors/cancer

Fertility problems

Osteoarthritis

Gout and

rheumatological

problems

Dermatological problems

Gastrointestinal

Problems

Cardiovascular disease

Mental/emotional problems

Respiratory disease

13

All-cause Mortality for Weight Change Patterns

For all participants, maintaining an obese

BMI from early adulthood to midlife

increased the risk of all-cause mortality

vs. stable normal weight, with an HR of 2.17 (95% CI, 1.85-2.53)

• Weight gain from a normal to overweight BMI was

not associated with risk, normal-obese (HR, 1.32;

95% CI, 1.15-1.52)

• Overweight to obese (HR, 1.47; 95% CI, 1.28-1.69)

weight changes were associated with elevated

mortality risks

JAMA Network Open. 2020;3(8):e2013448.

Estimated 12.4% OF EARLY DEATHS

may be attributable to having weight in

excess of the normal BMI range at any

point between early and mid-adulthood (95% CI, 8.1%-16.5%)

14

Why is it so Hard to

Lose Weight?

15

Neuronal and hormonal pathways influencing food intake and satiety in the brain

Srivastava G and Apovian CM. Nat Rev Endocrinol. 2018 Jan;14(1):12-24.

161.Yu JH et al. Diabetes Metab J. 2012;36(6):391-398.2.Mendieta-Zerón H et al. Gen Comp Endocrinol. 2008;155:481-495.

CNS, central nervous system

PfC, prefrontal cortex NAc, nucleus accumbens

VTA, ventral tegmental area

PP, pancreatic polypeptide

CCK, cholecystokinin; GLP-1, glucagon-like peptide 1

OXM, oxyntomodulin

PYY, peptide YY.

Primarily based on data from animal studies. Appetite Stimulating

Appetite Suppressing

Adapted with permission from Mendieta-Zerón H et al.2

Complex Peripheral Signals are Integrated into CNS Systems to Regulate Body Weight

Peripheral signals

are relayed to brain

systems via blood

and vagus nerve 1,2

Brain systems (homeostatic and

reward) receive and integrate

peripheral and other CNS

signals (eg, dopamine,

serotonin)1,2

Leptin, insulin, and ghrelin are integrated

directly into hypothalamus

VTA

Striatum

PfC

Hypothalamus

NAc

Hindbrain

Peripheral signals

are released

by pancreas,

gastrointestinal

system, and

adipose tissue1,2

17

Obesity Associated with Hypothalamic Injury in Rodents and Humans• Rodent models of obesity, induced by consuming high-fat diet (HFD), are

characterized by inflammation both in peripheral tissues and hypothalamic areas critical for energy homeostasis

• Unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain

• Both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding

• Evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI

Thaler PT, et al. J Clin Invest. 2012 Jan 3;122(1):153-62. doi: 10.1172/JCI59660. Epub 2011.

Findings suggest obesity is associated with neuronal injury

in a brain area crucial for body weight control

in both humans and rodent models

18

Translation of Defense of the

Body Weight Set Point:

Body continues to fight against weight loss long

after dieting has stopped

• 2009, 50 obese men and women

• Men 233 lbs/average Women 200 lbs/average

• Extreme low-calorie diet

• Optifast shakes + 2 cups of low-starch vegetables

• Total 500-550 kcal/d for eight weeks

Sumithran P et al. N Engl J Med. 2011;365:1597-1604.

• At 10 weeks: 30-lb ave. weight loss

At year one: 11-lb ave. weight regain

• Reported feeling more hungry and preoccupied

with food than before the weight loss

19

14% Weight Loss Produced Changes in Eight Hormones That Encourage Weight RegainMean fasting and postprandial levels of some peripheral signals at baseline and 62 weeks

Reduced Increased

Leptin - 65%

Peptide YY

Cholecystokinin

Insulin

Amylin

Ghrelin

Pancreatic polypeptide

Gastric inhibitory

polypeptide

Measures of appetite

10-week, lifestyle-based weight loss intervention in healthy overweight and obese adults (n=34)

Led to sustained elevations in appetite stimulating hormone(s) and decreases in appetite suppressing hormones

Sumithran P et al. N Engl J Med. 2011;365:1597-1604.

20

Long-Term Persistence of Hormonal

Adaptations to Weight LossChanges in Weight

from Baseline to

Week 6230-lb LOSS

11-lb GAIN

10 week weight-loss

program

Sumithran P et al. N Engl J Med. 2011;365:1597-1604.

21

Obesity Guidelines

22

2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and The Obesity Society

July 1, 2014

J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023.

23

• Prescribe set number of calories per day

• There is no ideal diet

• Advise obese adults who meet criteria that surgery may be an option

2013 Guidelines: Recommendations

• Use BMI to identify risk; advise patients of their risk

• Use waist circumference to identify risk; advise patients of their risk

• 3%-5% sustained weight loss reduces risk factors and risk of diabetes

J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023.

2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults

24

Prescribe a diet to achieve reduced calorie intake for obese or

overweight individuals who would benefit from weight loss, as part

of a comprehensive lifestyle intervention. Any one of the following

methods can be used to reduce food and calorie intake:

• 1,200–1,500 kcal/d for women

• 1,500–1,800 kcal/d for men (adjust for individual’s body weight);

• 500 or 750-kcal/d energy deficit

Prescribe SET NUMBER OF CALORIES/DAY

Obesity Guidelines: Recommendation 3

• Prescribe one of the evidence-

based diets that restricts certain

food types (such as high-carb

foods, low-fiber foods, or high-fat

foods) in order to create an energy

deficit by reduced food intake

2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults

Choose an evidence-based diet –there is NO IDEAL DIET

J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults

2021

Flexitarian

Diet

Best for weight loss

flexible and vegetarian

25

LAGB surgeryStomach

Appetite Suppressing

DRUGSHypothalamus

DRUG:

Lipase Inhibitors (Orlistat) Intestines

Gastric Bypass, BPD

Gastric Sleeve surgeriesIntestines

Where Obesity Treatments Work

Source of photo: Mendieta-Zerón H1, López M, Diéguez

C.Gen Comp Endocrinol. 2008 Feb 1;155(3):481-95.

26

0% 5% 10% 15% 20% 25% 30% 35%

Weight Loss

Problem: Treatment Gap in Mid-BMI Range

NOT EFFECTIVE enough

for many people

After Aronne L. FDA EMDAC 2010.

DIET AND LIFESTYLE

& DRUGS

Lap BandGastric Bypass BPD

Sleeve gastrectomy

Treatment

Gap

How to fill this gap?

TOO RISKY for many people

BARIATRIC SURGERY

27

Anti-obesity

Medications

28

Rationale for Obesity Pharmacotherapy

• Obesity causes more than 200 other medical disorders that affect entire organ systems

• Accounts for ~4 million deaths worldwide and a high cardiovascular disease burden

• Prevalence is rapidly increasing

Highlights the immediate need for

early recognition and treatment

in the context of the

existing available therapeutic armature

Srivastava G and Apovian CM. Nat Rev Endocrinol. 2018 Jan;14(1):12-24.

29

Medical Treatment for Obesity vs T2DM

CDC, National Center for Health Statistics, Division of Health Interview Statistics, data from the National Health Interview Survey.

Cowie CC, et al. Diabetes Care. 2009 Feb;32(2):287-94.

Samaranayake NR, et al. Ann Epidemiol. 2012 May;22(5):349-53.

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

Obesity Type 2 Diabetes

U.S

. A

du

lt P

op

ula

tio

n (

%) Adults in the U.S.

Indicated Treated

30

Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline

January 15, 2015

Apovian CM, Aronne LJ, Bessesen D, et al. J Clin Endocrinol Metab. 2015 Feb;100(2):342-62.

31

FDA Approval Criteria: Anti-obesity Drug

• Standard guidelines were issued in the mid-1990s

• A new drug must induce statistically significant placebo- adjusted

weight loss of:

• >5% at 1 year or

• >35% of patients should achieve >5% weight loss

(which must be at least twice that induced by placebo)

• In addition, the medication is required to show evidence of

improvement in metabolic biomarkers, including blood pressure,

lipid levels and glycemic control

www.fda.gov/downloads/Drugs/Guidances/ucm071612.pdf

32

FDA Approves New Drug Treatment for Chronic

Weight Management, First Since 2014

• Approved June 04, 2021

• Indicated for chronic weight management in patients with BMI > 27 kg/m2 with at least one weight-related ailment or BMI > 30 kg/m2

• Works by mimicking GLP-1, targeting areas of the brain that regulate appetite and food intake• Dosing must be increased gradually over 16 to 20 weeks to 2.4 mg

once weekly to reduce gastrointestinal side effects

• N = >2,600 patients up to 68 weeks in four studies with >1,500 patients receiving placebo

https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014

33

FDA Approves New Drug Treatment for Chronic

Weight Management, First Since 2014

Trial of pts without diabetes:• 46 years average age• 74% female• 231 lbs (105 kg) average body weight • 38 kg/m2 average BMI • Lost average of 12.4% initial body weight vs. placebo

Trial of pts with type 2 diabetes:• 55 years • 51% were female• 220 lbs (100 kg)• 36 kg/m2 average BMI• Lost 6.2% of initial body weight vs. placebo

https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014

Adverse Effects

nausea, diarrhea,

vomiting, constipation,

abdominal pain,

headache, fatigue,

dyspepsia, dizziness,

abdominal distension,

eructation,

hypoglycemia) in

patients with type 2

diabetes, flatulence,

gastroenteritis,

gastroesophageal

reflux disease

34

Effects of Once-Weekly Semaglutide vs. Placebo, on Body Weight

• Significant reduction in body

weight from baseline

• –14.9% semaglutide group vs.

–2.4% placebo group

• Greater mean weight loss

• –15.3 kg semaglutide group vs.

–2.6 kg placebo group

• Greater weight loss of at least 5%

• 86.4% in semaglutide group vs.

placebo (31.5%)

Wilding JPH, et al. N Engl J Med. 2021 Mar 18;384(11):989.

35

Efficacy of Current Anti-obesity Drugs

Indicated to be used as adjuncts to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a BMI ≥30 kg/m2 or

those with a BMI ≥27 kg/m2 who have at least one weight-related comorbid condition such as diabetes mellitus, hypertension, hyperlipidemia or sleep apnea

Srivastava G and Apovian CM. Nat Rev Endocrinol. 2018 Jan;14(1):12-24.

Wilding JPH, et al. N Engl J Med. 2021 Mar 18;384(11):989.

7.5/46 mg for 1 year

15 mg daily for 28 wks

Maximum dose for 56 wks

3.0 mg for 56 wks

120 mg thrice daily for 1 year

Phentermine/topiramate ER(Gadde et al. 2011)

Phentermine(Aronne et al. 2013)

Naltrexone SR/bupropion SR(Greenway et al. 2010)

Liraglutide (Saxenda)package insert 2014

Orlistat(Aronne et al. 2013)

Semaglutide (Wegovy)(Wilding et al. 2021) 2.4 mg once weekly injection for 68 wks

0 1 2 3 4 5 6 7 8 9 10 11 12 13

% Estimated weight loss (drug minus placebo)

37

Current Obesity Pharmacotherapy for Long-term Use

5-HT2c=serotonin; DA=dopamine; GLP-1=glucagon-like peptide-1; MOA=mechanism of action; NE=norepinephrine.

1. Yanovski SZ et al. JAMA. 2014;311:74-86. 2. Apovian CM et al. J Clin Endocrinol Metab. 2015;100:342-362.

3. Kim GW et al. Clin Pharmacol Ther. 2014;95:53-66. 4. Dietrich MO et al. Nat Rev Drug Discov. 2012;11:675-691.

Intestines

OrlistatLipase inhibitor

Phentermine/topiramateSympathomimetic amine + antiepileptic

Liraglutide and NEW Semaglutide

GLP-1 receptor agonist

Naltrexone/bupropionµ-opioid antagonist +

DA/NE reuptake inhibitor

Mesolimbic Reward System

Hypothalamus

Hypothalamus

Hypothalamus

Dorsal Vagal

complex

Mesolimbic

Reward System

Hypothalamus

Dorsal Vagal

Complex

38

Pharmacotherapy Increases Magnitude and Likelihood of Weight Loss

Pucci A, et al. Can J Cardiol. 2015;31(2):142-152. Astrup A, et al. Int J Obes (Lond). 2012;36(6):843-854.

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39

Long-term Ongoing Therapy Needed for

Obesity Treatment

Schalles, et al. Visc Med. 2016, figure adapted by Ania Jastreboff, MD, PhD.

AOM

stopped

NEW –

borrowed from

Ivania Rizo

40

Effective Ineffective

Loss of ≥5% body weight

at 3 months and

medication is

safe/tolerated

Loss of <5% body weight

at 3 months or

safety or tolerability issue

with medication

Continue medication • Discontinue medication

• Seek alternate

medication or refer for

alternative therapy

Apovian C, Aronne LJ, et al. J Clin Endocrinol Metab. 2015 2015 Feb;100(2):342-62.

Medications: Assessing Efficacy and Safety

41

Adding

Pharmacotherapy

to Bariatric Surgery

42Ikramuddin S, et al. Lancet Diabetes Endocrinol. 2015 Jun;3(6):413-22.

Surgery: Better Weight Loss than Lifestyle and Medical MngtThe Diabetes Surgery Study Randomized Clinical Trial

7.3%

23.8%

Difference, 17%95% CI, 13-20%

43

Vertical Banded Gastroplasty

Gastric Bypass

Nonadjustable or Adjustable

Surgery: Best Long-term Weight Loss Results

Sjöström L. J Intern Med. 2013 Mar;273(3):219-34.

% Weight Change: -18% mean change in body weight over 20 years

44

3540

35

6055

6558

50

82 78

6268

0

10

20

30

40

50

60

70

80

90

Diabetes HTN Sleep Apnea GERD

Band Sleeve Bypass

Resolution or Improvement in Comorbidities Varies by Type of Surgery

Hutter et al. Ann Surg. 2011 Sep;254(3):410-20; discussion 420-2.

% R

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r Im

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nt

N = >28K x 3 years

45

Sleeve Gastrectomy Gastric Bypass

• Average weight loss:

– 30% of total weight

• Surgery takes about 90-120 minutes

• 1-2 days in hospital

• Limits ingestion of food and changes hunger signals

• Reversible in extreme cases

Gastric Band (LAP-BAND)

• Not commonly performed as weight loss results have not been optimal in the long-term

• Our team will consider this operation on a case-by-case basis

Bariatric Surgery Procedures

• Average weight loss:

– 25% of total weight

• Surgery takes about 60 minutes

• 1 day in hospital

• Limits ingestion of food and changes hunger signals

• Non-reversible

46

The Problem

Patients who undergo bariatric surgery often have:

– Inadequate weight loss (<20% of total body weight loss), or

– Weight regain post surgery (≥15% gain of initial weight loss)

Two Studies

Discern the utility of weight loss pharmacotherapy as an adjunct to bariatric surgery and tool to prevent weight regain

Stanford FC, Aronne LJ, ET AL. Surg Obes Relat Dis. 2017 Mar;13(3):491-500. Istfan NW, Apovian CM, et al. Obesity (Silver Spring). 2020 Jun;28(6):1023-1030.

47

Phentermine and Topiramate Reduce theOccurrence of Rapid Weight Regain after RYGB

Phentermine and

topiramate, used

individually or in

combination, can

significantly reduce

WR after RYGB

Istfan NW, Apovian CM, et al. Obesity (Silver Spring). 2020 Jun;28(6):1023-1030.

N= 760

350 (46.1%) used AOMs

• 119 (34.0%) phentermine

• 74 (21.1%) topiramate

• 154 (44.0 %) combination

of phentermine and

topiramate

48

Design

• Retrospective study 2000-2014

Setting

• 2 Academic Institutional Practices

Patients and Other Participants

• Patients who had undergone Roux-en-Y gastric bypass (RYGB) or a vertical sleeve gastrectomy (VSG) who were subsequently placed on weight loss pharmacotherapy post-operatively

• Of the 5110 charts reviewed, 319 met inclusion criteria

Interventions

• Weight loss pharmacotherapy: 15 FDA and non-FDA approved meds

Stanford FC, Aronne LJ, et al. Surg Obes Relat Dis. 2017 Mar;13(3):491-500.

Utility of Weight Loss Medications After Weight Loss Surgery

N=319 patients

• RYGB = 258

• Sleeve gastrectomy = 61

49

Results• 54%, n=172 of all study patients lost ≥ 5% of their total body weight with

post-surgery weight loss pharmacotherapy

• High responders: • 30.3% (n=96) lost ≥ 10% of their total body weight

• 15% (n=49) lost ≥15% of their total body weight

• Topiramate – the only medication demonstrating statistically significant weight loss with patients being twice as likely to lose at least 10% of their weight (OR=1.9, p=0.018)

• RYGB patients were significantly more likely to lose ≥ 5% of their total body weight with the aid of weight loss medications vs. VSG patients (regardless of postop BMI)

• Total body weight loss from surgery plus weight loss pharmacotherapy

• 26.8% (SD=10.5) [4.3-60.2%] patients starting meds after weight regain

• 32.3% (SD=11.4) [8.3-56.3%] patients starting meds at their weight plateau after bariatric surgery (p=0.486)

Utility of Weight Loss Medications After Weight Loss Surgery

Stanford FC, Aronne LJ, et al. Surg Obes Relat Dis. 2017 Mar;13(3):491-500.

50

Demonstration of the utility of weight loss mediation after bariatric surgery in a RYGB patient

Stanford FC, Aronne LJ, et al. Surg Obes Relat Dis. 2017 Mar;13(3):491-500.

51

Keys for Long-term

Success

52

Long-term Weight Loss

Long-term treatment with regular supportcan be effective1-5

Weight must be managed on an ongoing basis5-9

1. Elmer PJ, et al. Annals of Internal Medicine, 144:485–495, 2006.

2. Wadden TA. Annals of Internal Medicine, 119(7):688–693, October 1993.

3. Tate DF. JAMA, 289(14):1833–1836, April 9 2003.

4. Tate DF, Wing RR, Winett RA. JAMA 285(9):1172–1177, March 7 2001.

5. Ness-Abramof R, Nabriski D, Apovian CM. The Israel Medical Association Journal, 6:760–765, December 2004.

6. Wadden TA, Brownell KD, Foster GD. Journal of Consulting and Clinical Psychology, 70(3):510–525, 2002.

7. Wadden TA, Foster GD, Letizia KA. Journal of Consulting and Clinical Psychology, 62(1):165–171, 1994.

8. Wadden TA, et al. Archives of Internal Medicine, 161:218–227, 2001.

9. Wadden TA, et al. NEJM, 353(20):2111–2122, November 2005.

53

Frequent Patient Follow-up is Key

JAN FEB MAR APR MAY JUNE JULY AUG SEPT OCT NOV DEC

All patients prescribed weight loss medications:

At least monthly for first 3 months

Then at least every 3 months

Centers for Medicare & Medicaid Services coverage:

Month 1 Four visits (1 per week)

Months 2-6 One visit per month

if 3 kg (6.6 lbs) lost, then:Month 7-12 One visit per month

www.cms.gov Decision Memo for Intensive Behavioral Therapy for Obesity (CAG-00423N).

15 visits per year

54

Bariatric Surgical Patients Require Lifelong Follow-up Visits

Encourage All patients are encouraged to drink water long-term

Consumption of lean protein sources is encouraged

Vitamin and mineral supplementation should be reinforced at every visit to avoid micronutrient deficiencies

Routine exercise should be encouraged

• Walking is an appropriate way to start exercising

• Patients with degenerative joint disease may benefit from aquatic exercise to reduce joint pain

https://www.uptodate.com/contents/bariatric-surgery-postoperative-and-long-term-management-of-the-uncomplicated-patient

Processed snack foods and sweetened beverages are discouraged because they increase calorie intake unnecessarily

Carbonation and straws because of the risk of gastric bloating

Discourage Caffeinated beverages should be avoided because of the diuretic effect

55

Successful Long-term Weight LossNational Weight Control Registry: Lifestyle Changes

• 10,000 registrants

• Maintaining 66 lb loss for 5 years

• Eat 1800 kcal/day with 27% fat

• Perform 2700 kcal/week exercise

• 40% weigh themselves daily

• 20% weekly

• Reduced TV watching

• Limit diet variety

• 78% eat breakfast

• Eat fast food once per week

• Use more artificially sweetened beverages than others of normal weight

• They are VIGILANT

Ten Year NWCR Data

• N=2886 who lost 31 kg maintained for 5 years

• Regain at end of 10 years but still lost 30% total body weight then gained to 22.6% total weight loss

• 10 year loss = 23 kg (50.6 lbs)

• Weight regain levels out from 5 years to 10

• 85% of registrants lost 20%

• 40% of registrants lost 30%

• If exercise decreased by 500 kcal per week they regain 9 kg

• If exercise is maintained they regain only 4.5% or 4.5 kg

National Weight Control Registry http://www.nwcr.ws/ Thomas JG, et al. Am J Prev Med. 2014 Jan;46(1):17-23.

56

Maintaining Weight LossNational Weight Control Registry

N=2886

Mean weight loss:

Baseline: 31.3 kg (95% CI=30.8, 31.9)

5 Years: 23.8 kg (95% CI=23.2, 24.4)

10 Years: 23.1±0.4 kg (95% CI=22.3, 23.9)

>87% were estimated to be maintaining >10% weight loss at Years 5 and 10

Better long-term outcomes with:

• Larger initial weight losses

• Longer duration of maintenance

Greater weight REGAIN associated with:

• Decreases in leisure-time physical

activity

• Decreases in dietary restraint

• Decreases in self-weighing frequency

• Increases in percent of intake from fat

and disinhibition

http://www.nwcr.ws/

Thomas JG, Bond DS, Phelan S, Hill JO, Wing RR. Am J Prev Med. 2014 Jan;46(1):17-23.

57

Percentage Weight Loss by Minutes of Physical Activity (calories per week)

Wadden TA, et al. Circulation. 2012;125:1157-70.

Total n=170

maintained 3xthe weight loss

vs. those at 150 min/wk

= >2000 kcal/wk)

= >1000 kcal/wk)

58

• Consistent finding in four 2012 meta-analyses, each summarizing 13 to 24 trials: adherence was most strongly associated with weight loss1-4

• Meta-analysis 2014: 48 trials, n = 7,286; conclusion: any diet a patient will adhere to lose weight is best5

1. Ajala O, English P, Pinkney J. Am J Clin Nutr. 2013 Mar;97(3):505-16.

2. Wycherley TP, et al. Am J Clin Nutr. 2012 Dec;96(6):1281-98.

3. Hu T, et al. Am J Epidemiol. 2012 Oct 1;176 Suppl 7:S44-54.

4. Bueno NB, et al. Br J Nutr. 2013 Oct;110(7):1178-87.

5. Johnston BC, et al. JAMA. 2014;312(9):923-933.

Adherence - Not Diet - Predicts Success

59

Barriers to Success

60Adapted from Aronne LJ, Segal KR. J Clin Psychiatry. 2003;64(Suppl 8):22-29. Leslie WS, et al. QJM. 2007;100(7):395-404. Messerli FH, et al. Am J Med. 2007;120(7):610-615.

Drugs That Tend to Promote Weight Gain, Weight Loss, or Are Weight Neutral

• Exenatide, liraglutide, pramlintide

• Sitagliptin

• Metformin

• Acarbose, miglitol

• Canagliflozin

Weight LOSS or Weight NEUTRAL

Diabetes Treatments

• Insulin

• Sulfonylureas

• Thiazolidinediones

Diabetes Treatments

Weight GAIN

• Antipsychotics

• Antidepressants

• Antiepileptics

• Lithium

Psychiatric/Neurologic

• Ziprasidone, aripiprazole

• Bupropion

• Topiramate, zonisamide, lamotrigine

Psychiatric/Neurologic

61

Ultra-processed FoodsMay Facilitate Overeating

• Rise in obesity and type 2 diabetes prevalence

occurred in parallel with increasingly industrialized

food system

• Large scale production of high yield, inexpensive,

agricultural “inputs” (corn, soy, wheat), refined and

processed

• Highly processed foods, with added amounts of fat

and/or refined carbohydrates (e.g., sugar, white

flour), were most likely to be associated with

behavioral indicators of addictive-like eating

• Additionally, foods with high GL were especially

related to addictive-like eating problems for

individuals endorsing elevated symptoms of “food

addiction”

Poti JM, et al. Curr Obes Rep. 2017 Dec;6(4):420-431.

Schulte EM, et al. PLoS One. 2015 Feb 18;10(2):e0117959.

How Often Food was

Selected as ProblematicTop 10 of 35

Food Ratings Based on

7-point Likert ScaleNot Problematic to Extremely

Top 10 of 35

62

• 20 inpatient adults received ultra-

processed and unprocessed diets

for 14 days each

• Diets were matched for presented

calories, sugar, fat, fiber, and

macronutrients

• Ad libitum intake was ~500

kcal/day more on ultra-processed

vs unprocessed diet

• Body weight changes were highly

correlated with diet differences in

energy intake

Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain

Hall KD, et al. Cell Metab. 2019 Jul 2;30(1):67-77.e3.

63

0% 5% 10% 15% 20% 25% 30% 35%

Weight Loss

Treatment Gap in Mid-BMI Range

NOT EFFECTIVE enough

for many people

After Aronne L. FDA EMDAC 2010.

DIET AND LIFESTYLE

& DRUGS

Lap BandGastric Bypass BPD

Sleeve gastrectomyPrior to 2012:

Orlistat Phentermine

Treatment

Gap

Drug options:Liraglutide

NEW Semaglutide

Combination Pharmacotherapy

Phen/topNalt/bup

Less Invasive Procedures

Vagal block therapyEndoscopic sleeve

The gap is being filled

New drugs and devices can reduce weight and weight-related comorbidities

TOO RISKY for many people

BARIATRIC SURGERY

64

Summary

• Overweight and obesity are measured by Body Mass Index (BMI)

• 42.4% of U.S. Adults have obesity

• 30.7% of U.S. Adults are overweight

• Lifestyle interventions can be effective with long-term follow-up

• Bariatric surgery is the most effective form of long-term weight loss

• Weight regain occurs in 17-30% of RYGB patients at two years post-op

• Anti-obesity medications are effective at increasing post-op weight loss and preventing weight regain

• New GLP-1 agonist, semaglutide, shows promise to help fill BMI-mid-range treatment gap

65

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